Zaidi Biochem Flashcards
What are some functions of the liver?
Carbohydrate metabolism- glucostasis
Lipid metabolism
Nucleotide biosynthesis and AA metabolism
Waste management- inactivate and detox
How many acetyl-coa are used to create IPP?
What are IPPs the building blocks of?
3 acetyl-coa are used to create a 5 carbon IPP
IPP are building blocks for isoprenoids such as steroids, vitamins, and prenyl groups
What are the sources of acetyl-coa that are used for IPP synthesis?
Oxidative decarboxylation of pyruvate, beta oxidation of FA, and AA metabolism
What is phase 1 of cholesterol synthesis?
What is the rate limiting step/enzyme?
Acetyl-CoA, acetoacetyl-CoA, HMG CoA (via HMG CoA synthase), mevalonate (via HMG CoA reductase-rate limiting), IPP
HMG CoA to mevalonate is rate limiting step which is catalyzed by HMG CoA reductase
What is phase 2 of cholesterol synthesis?
IPP x 6, squalene, lanosterol, desmosterol, cholesterol
What drug inhibits the rate limiting step of cholesterol synthesis? How does it work? What are some side effects?
Statins inhibit the conversion of HMG CoA to mevalonate by binding the active site of HMG CoA reductase with high affinity
Potential myotoxic side effects include deficiency of CoQ10 (ubiquinone)
What are the fates of cholesterol?
Incorporate into membrane
Used in synthesis of vitamin D
Used in synthesis of steroids
Used in synthesis of bile salts
What are examples of late stage inhibitors of cholesterol synthesis and where do they act?
Antimycotics- inhibit production of ergosterol which is major constituent of fungal membranes
Anti-epileptics- inhibit squalene to lanosterol
Anti-estrogens- inhibit desmosterol to cholesterol
Why can cholesterol not be degraded?
No enzyme can degrade the sterane ring
What is the function of bile salts?
Bile emulsifies lipids and incorporates them into micelles to increase SA for lipase action
Explain the synthesis of bile salts
Cholesterol, 7alpha hydroxycholesterol (via 7ahydroxylase- now has 2 hydroxyl groups), Cholic acid (now has 3 hydroxyl groups), Cholyl CoA
Cholyl CoA + glycine= glycocholic acid
Cholyl CoA + taurine= taurocholic acid
What do bile acid binding resins do? How do they lower LDL levels?
Bile acid binding resins such as cholestryamine are used to lower LDL levels by interrupting the enterohepatic circulation and decrease bile reabsorption which induces 7ahydroxylase activity which increases conversion of cholesterol to bile
What are gallstones? Why may a patient develop steatorrhea?
Gallstones are crystals of bile supersaturated with cholesterol
Chronic disturbance in metabolism of bile salts disrupts lipid absorption which leads to fatty stools
What are metabolites?
What are xenobiotics?
Metabolites are products made by the body
Xenobiotics are products ingested that do no have any nutritional value
What is the purpose of phase 1 rxn of xenobiotic detox?
What is the purpose of phase 2 rxn of xenobiotic detox?
What enzymes are responsible for these rxn?
Phase 1 rxn- increase polarity
Phase 2 rxn- conjugate functional groups
Cytochrome P450 enzymes
